"Inugami-san to Nekoyama-san" is a short-form anime series based on the 4-panel manga by Kuzushiro. The narrative centers on the comedic and lighthearted interactions between two high school girls, Yachiyo Inugami and Suzu Nekoyama, whose personalities and behaviors are heavily influenced by their animal-like traits. Inugami, whose name and demeanor reflect a dog, is energetic, loyal, and prone to impulsive actions, while Nekoyama, embodying cat-like traits, is aloof, lazy, and enjoys being pampered. Their contrasting personalities create a dynamic and humorous relationship as they navigate daily school life.

The series explores their growing friendship and the quirky situations that arise from their animalistic tendencies. Inugami often seeks Nekoyama's attention, displaying her dog-like devotion, while Nekoyama, true to her cat-like nature, alternates between indifference and playful teasing. Their interactions are further enriched by the presence of other characters, such as Ushikawa, a cow-like girl who is shy and easily flustered, and Aki, a more grounded and observant classmate who often serves as a mediator in their antics.

The plot is episodic, with each short episode focusing on humorous scenarios that highlight the characters' animal-inspired traits and their relationships. Themes of friendship, acceptance, and the playful exploration of human-animal parallels are woven throughout the series. The humor is largely derived from the exaggerated animal behaviors and the contrast between Inugami's exuberance and Nekoyama's calm detachment. The series maintains a light, comedic tone, with no overarching conflict or dramatic tension, making it a straightforward and enjoyable slice-of-life anime.